2-amino-and 2-alkylthio-4-(2-furyl)-thiazoles



Patented Sept. 13, 1949 UNITED STATES PATENT OFFICE z-nMmo- AND Z-ALKYLTHIO- l- (anon m- THIAZOLES v Edward B. Knott, Frances M. Hamer, and'Russell J. Rathbone, Harrow, Wealdstone, England, as

signors to Eastman Kodak Company, R'oches ter, N. Y., a corporation of New Jersey N Drawing. Application February '7, 1946, Serial No. 646,207. In Great Britain March 1,1945

This invention relates to 2-aminoand z-alkylthio-4- (2-furyl) thiazoles.

The 2-aminoand 2-alkylthio-4-(2-iuryl) thiazoles of our invention can be represented by the following general formula:

wherein R represents a 2-furyl group, substituted or not substituted, and R represents a hydrogen atom or-an alkyl group, e. g. methyl, ethyl, isopropyL- n-butyl, etc. or an aryl group, e. g. phenyl, p-chlorophenyl, etc., with a thioamide of the following general formula:

III. N

- X-C-NH:

wherein X has the values given above. Typical thioamides which we employ in practicing our invention are: thiourea, and S-alkylor S-aralkyldithiocarbamates, e. g. methyl dithiocarbamate, ethyl dithiocarbamate, n-propyl dithiocarbamate, isobutyl dithiocarbamate, benzyl dithiocarbamate, etc.

The condensation proceeds smoothly in all 1 cases upon heating the 2-(a-halogenoacyDfuran and the thioamide together, advantageously in a solvent, e. g. methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, isobutyl alcohol, n-butyl alcohol, etc. The condensations take place rapidly at elevated temperatures and are accelerated by the addition of alkalies, e. g. alkali metal carbonates, e. g. sodium or potassium carbonate. Alkali metal bicarbonates, e. g. sodium or potassium bicarbonate, also accelerate the condensations.

The following examples will serve to illustrate further the manner of practicing our invention:

8 Claims. (01460-302) Eaiample'i -2-amino-4- (Z-Iuryl) thiaeole Thiourea (3.8 g.) 2-chloroacetylfuran (7.22 g.) and ethyl alcohol (50 cc.) were heated carefully until a solution formed. Anhydrous sodium carbonate (2.6 g.) was then added to the solution which was then refluxed for 5 minutes. Upon adding water the .2-ainino-4-(2-furyl)thiazole separated as glistening crystals. The thiazole derivative was filtered off and recrystallized from a mixture of benzene and petroleum ether. It was obtained as glistening buii needles, melting at 124.5 C.

Methyldithiocarbamate V (2.6 g.), Z-bromoacetylfuran (4.5 g.) and ethyl alcohol (10 cc.) were warmed gently. Reaction occurred andthe hydrobromide of 4-(2-furyl) -2-methylthiothiazoleprecipitated. The mixture was chilled and 50 cc. of diethyl ether were added. The hydrobromide was then collected on a filter. It was recrystallized from a mixture of ethyl alcohol and ether and obtained as glistening shiny plates, melting at 206 to 210 C. The hydrobromide was dissolved in aqueous ethyl alcohol. The solution was diluted with aqueous sodium carbonate solution, and the 'oil' which precipitated was taken up in diethyl ether. The ether extract was dried and distilled. 4-(2-furyl) -2 -methylthiothi azole distilled at 17.7 C. at 18 mm. of Hg pressure; It was obtained 'as a'thick oil, having a mushroomlike odor. I

In a manner similar to that illustrated in Ex-'- ample 2, '2-butylthio-4-(2-furyl) thiazole, 2-' benzylthio-.4-(Z-furyDthiazole and z-ethylthio- 4-(2-furyl)thiazole can be prepared using butyldithiocarbamate, benzyldithiocarbamate and ethyldithiocarbamate respectively.

The 2 -(a-halogenoacyl) furans can be prepared by a modification of the procedure described by Burger and Harnest, J..Am. Chem. Soc. 65, 2382 (1 943), These'authors describe 2-chloroacetylfuran as an oil, but I have obtained it in crystalline form as shown in the following example.

' Example 3.2-chloroacetylfuram TIC-H o Furoyl chloride was converted to 2-diazoace-- gen chloride, 2-bromoacetylfuran was obtained,

boiling at 126 C. at 18 of Hg pressure. Recrystallized fromka mixture; of benzene a d; p troleum ether, it melted at 34 C. (colorless plates).

The present invention alsoxincludes the formation of quaternary salts by heating. any of the thiazole derivatives represented by Formula I with an alkyl salt or an aralkyl salt, 8. g. an alkyl ha eb -hut lbromi et l iodide, pr y de blltr 'bmm danebuty ch o ide, benzyl bromide. etc. Q-an alkyl-p-toluenesulfonate, e. g. methyl p-toluenesulfonate, ethylip-toluenesulfonate, 'etc. a dialkylsulfate, e; g. dimethyl sulfate,fdiethyl sulfate, etc;

The following examplesjwill'srve to illustrate further the manner of, obtaining these quaternary salts:

Example 41 4'- (-2 -faint?-2mthylthithiazole methiodide -f rrh g methvlthiot a ole. 3 62 a; 1 mol.) and methyl-p-tolunesulfonate (3.92 g.; 1 mol.) were heated together in an oil bath at 140 C. for 1 hour. The thiclsmeltof. 41-(.2-furyl) -2- methylthiothiazole. v V was diluted with water" '(5 00.) and poured into a solution of potassium iodide (6.6 g.; 2 mols.) in water 9 00,) The crystals of 4- (2 -furyl) -2- inethylthiothiaizol'e" metlriodide which precipitated were collected m} washed with a little ethyl alcohol;

Example 5. -4Z#f1wyl )-2-methylthiethiazole etho-p-to'menesztlfoncte' 4- 2-furyni-ametn 1t btmazo1e I (3.15 I g.; 1 mol.) and ethyl-ptoluenesulfonate (3.19 g.,; 1 mol.) were heated together in an oil bath at 120- 1l0 C. for 6 hoursresuItingQ-(Z-furyD -2- methyl-thiothiazole qethd-p-toluenesulfonate was washedv with. absolute diethyl ether. Itlwas'. in the form of a-li ght. -brow-rgum. and. was water soluble. v

As shown Example 51;, the anion ofthe quaternary Saltohtai'ned .i'nlthe original heating can be changed and a less soluble quaternary salt produced. bytreating a. solution of the more solublequaternary salt-(in. an alcohol or water). with anaqueous solutionef. awater-soluble metal salt. Thus. using-sodium or potassium iodide, bromida perohlorate or rhodanate, the. quaternary iodides, bromideaperehloratesor rhodaatescan. be prepared from the quaternary chlorides, p toluenesulfonates or alkylsulfates. The new quaternary, saltswof our invention can be represented-bythezfollowing, generalfo'rmula;

metho-r-p-tolnenesulfonate -'cyclic compoundscon-taining 'in the ring the folwherein R, R and X have the values given above,

R2 represents an alkyl or aralkyl group and X1 7 represents an anion,

lowing group of atoms:

-o-omo wherein Q represents an-v la atom, a nv t m ar rou wherein Rs r p s n s. ahydr ee t m. m y

group, an aralkyl group; or an apyl groumtoegive merocyanine dyes of the following general for: mula:

v1. 0 l. it o i wherein R, R, R2 and Z Havethevalues-giveri above, and Z represents the non-metallicatoms necessary to complete a heteroeyelie nucleuse. 'g.

d'ione nucleus, a aanmnyeantom nucleus; a'2-diarylam'ino-4-ketothiazoline nucleus, a- 2-'(Nfalkyl-N-arylamino) -4-'letothfazoline' nucleus; a thiobarbituric acidnucleus, etc.

The condensations are advantageously efiected 4- (Z-furyl) 2 methylthiothiazole methiod ide (1.7 g.; 1 mol.) 3 ethylrhodanine.(0.81. g..; 111101.), triethylamine (LBS-.00.; 2- mols.): and ethyl al cohol (20 cc-) were boiled. together, while stirring, for 2 minutes The mixture. .wasallowed tocool and the above-formulated dye which had separated out was filtered off. The. dye 1 was washed with .water and. then with. etloiyl alcohol and finally. recrystallized ffronr methyl alcohol Example 7.--[ 5- (2 e diphehyldmino 4-lcetothiazoline) l-[2-{4-(2-juryl) '-3 ethylthiazoZe}l-mer- 4- (2-furyl) -2-methylthiothiazole' etho-p-toluenesulfonate (2.97 g.; 1 mol.), 2-diphenylamino- 4-ketothiazoline (2.01 g.; 1 mol.), triethlyamine (1.1 cc.; 2 mols.) and ethyl alcohol cc.) were boiled while stirring, for 3 minutes. The mixture was allowed to cool and the above-formulated dye separated out. It was filtered off and washed with water. The crude dye was boiled out with ethyl alcohol (30 cc.) and the residue was recrystallized from methyl alcohol 130 cc.). The pale yellow dye had a melting point at 281 C. (decomposition). The absorption maximum of its methyl alcoholic solution was at 400 m The dye sensitized a gelatino-silver-chloride emulsion with maximum sensitivity at 420 m the sensitization extending to 470 m In a manner similar tothat illustrated in Examples 6 and 7, other merocyanine dyes of Formula VI can be prepared, e. g. from the following components: l

. Our 1 new quaternary salts represented by Formula IV"wher.ein."X -.represents an alkylthio or aralkylthio group can'alsobe condensed, we have ro 11w c a m nium-quatem sa o taining a reactive methyl group" to give inonomethine cyanine dyes.

The condensations-are advantageously effected in the presence oi an acid-binding agent (basic condensing agent), e. g; a tertiary amine, such as a trialkylamine (trieth'ylamine tripropylamine, tributylamine," etc.), or an alkali metal carbonate (sodium carbonate, potassium carbonate; etc;).'- It is c'onvenient'to-effect the condensations in a. solvent, e. g 21.1'i a1'cohol;such as ethyl alcohol, n-propyl alcohol or isopropyl alcohol. Typical of the cyclammonium quaternary salts containing "reactive methyl groups are: 2-methylbenzothiazole ethiodide; 2 methylbenzoselenazole ethiodide, 2 methylbenzoxazole ethiodide, Z-methyl-}8-naphthothiazole metho-ptoluenesultonate, i2 -methyl w naphthothiazole etho-p-toluenesulfonate, quinaldine ethiodide, lepidine ethiodide, 4-(2-furyl)-2-methylthiazo1e methiodide, etc. v

4-(2-furyl) -2-methylthiazole methiodide can be prepared as follows: r

Example 8 4-(2-furyl)-2-methylthiazole (3.62 g.; 1 mol.) and methyl-p-toluenesulfonate (3.92 g.; 1 mol.) were heated together in an oil bath at C. for 1 hour. The thick melt of 4-(2-furyD-2- methylthiazole metho-p-toluenesulfonate was diluted with water (5 cc.) and poured into a solution of potassium iodide (6.6 grams; 2 mols.) in water (10 cc.). The crystals of 4-(2-furyl)-2- methylthiazole methiodide were collected and washed with a little alcohol. The 4-(2-furyl)-2-methylthiazole employed above was prepared as follows:

Thioacetamide (7.5 g.), 2-bromacetylfuran (18.9 g.) and ethyl alcohol (20 cc.) were warmed gently to give a clear solution. The liquor suddenly boiled and solidified on cooling. Diethyl ether (50 cc.) was added and the hydrobromide of 4-(Z-furyDZ-methylthiazole was collected on a filter. Recrystallized from a mixture of methanol and diethyl ether, the hydrobromide formed glassy needles, melting at 194-196" C. The hydrobromide was dissolved in water and theI-(2-. furyl) -2-methylthiazole liberated by adding aqueous sodium carbonate. The thiazole base was taken up in diethyl ether, the ether solution dried over anhydrous sodium sulfate and distilled. The 4- (Z-iuryl)-2-methylthiazole distilled at 128 C. at 15 mm. of mercury pressure. It was an oil with a strong thiazole odor. A We have also found that alkyl and aralkyl quaternary salts of 4-(2-furyl)-2-methy1thiazole can be condensed with diarylformamidines, e. g. diphenylformamidine, to give .2-(18-anilinovinyl- 1-(2.-furyl)thiazo1e quaternary salts. Suchv ,3-anilinovinyl derivatives can also be formed, we have found, by condensing the alkyl and aralkyl quaternary salts of 4-(2-furyl) -2-methylthiazo1e with an alkyl isoformanilide, e. g. ethyl isoformanilide, or with an alkyl isothioformanilide, e. g. ethyl isothioformanilide, or with a mixture'of an alkyl orthoformate, e. g. triethyl orthoformate and a primary aromatic amine or a secondary aromatic amine, e. g. aniline or methylaniline.

The following examples will serve to illustrate further the preparation of the fi-anilinovinyl derivatives.

Example 9.2( 18-anzlinovinyl) -4- (z-juryl) thiazole ethz'odide washed with water.

. furyl) thiazole ethiodid 2-;9-anilinovinyl-4-'(2 iuryl)thiazo1e et cal e (5.6 g.) was boiled withjaceticxanhydridefor l'5 minutes. After 'cooling,dieth'yljetherwas added. Theprecipitated s-acetanilidbvinyl de'r save was filtered off-- and; washed with "diethyl eth'fi Example 1 0. 2- (fi-dcetanilidovinyl) 4- 2-" ananero The auli: yellow solid had a melting pointer- C; with decomposition-. In Example 10, it is shown that the p-anilino vinyl derivatives can be acyl'ated with carboxylic anhydrides to give fi-acylan-ilinovinyl compounds. Propionic, butyric or benzoic anhydrides can be used for example to replace the acetic anhydride.

The p-anilinoyinyl or o-acetanilidovinyl derivatives carr be condensed with; cyclammonium quaternary salts containing a reactive methyl grouprto give: carbocyanine dyes. For example, condensation can be effected with Z-methylbenzothiazole ethiodide, 4-(2-furyl) -2 -me thylthiazole. metho-p-toluenesulfonate, 2-methylbenzoxazole ethiodide, qu-inaldine ethiodide, lepidine ethiodideetc.

The c-anilinovinyl or B-acetanilidovinyl derivativescan also be condensed with heterocyclic compounds containing a ketomethylene group to givemerocarbocyanine dyes. For example, condensation can be effiected with rhodanine, 3.-ethylrhodanine, 3-phenylrhodanine, v3-ethyl- 2,4(13'5) -oxazoledione, Z-thiohydantoin, '1,3-diphenyl-thi'ohydantoin, etc; Q r a Thev dyes: of our invention sensitize photographic silver halide'emulsions when incorporatedfltherein. i

In the preparation; of photographic emulsions containing our new dyes, it is only necessary to disperse the dyes in-the emulsions. The methods of incorporating-dyes" in emulsions are simple and well known to those skilled in the art. It is convenient to addthe dyes from solutions inappropriate solvents. Methanol has proven satisfactory as a solvent'for our new dyes. If desired acetone may also be employed where the solubiIity of the dyes in methanol is lower than desired.

Sensitization by means of our new dyes is, of course, directed primarily to the ordinarily 'employed" gelatino-silver-halide developing-out emulsions. The dyes are. advantageously incorporated in the washed, finished emulsions .and should, of course, be uniformly distributed throughoutthe emulsions. I The concentration of our new dyes in the-emulsion' can vary widely,'i. e. from about5 to about loflmgs. per liter of fiowable emulsion. The concentration of the, dye will vary according to the type of light-sensitive material in the-"emulsion and according to the effects desired. The suit-- able and most economical concentration for any given emulsion will. be apparent to those skilled in the art upon making the ordinar te'sts'and observations customarily used in the art of emulsionmakingz: I

Topreparea geIa-tino-silver-halide emulsion sensitized with one of our new dyes, the follow ing-procedure issatisfactory: A quantity ofthe dye is dissolved in methyl alcohol or other suitable solvent and a volume of this solution (which maybediluted with water) containing from 5 to 100 ings. of dye is slowly added to about 1000 cc. of a gelatino-silver-halide emulsion, with stirring. Stirring is continued until the dye is uniformly distributed throughout the emulsion. With most of our new dyes, tomgs; of dye per liter of emulsion suflices to produce the maximum sensitizing effect withv the ordinary gelatino-silverbromide (including bromiodide) emulsions. With fine grain. emulsions, which.- include most of the ordinarily employed gelatino-silver chloride emulsions, somewhat larger concentrations of dye maybe necessary tosecure the'optimmn sensitize ingefliect. I

a The above statements; are; only iliustrativeiand are not to be understood as'limitingour intone. tion in any sense;v as iti .heapparedt that our new dyes can be incorporated by other methods in many of the photographic silver halide emulsions customarily employed'in the art; orm

stance, the dyes may be incorporated bybathing a plate or film upon which an emulsion has been coated, in the solution of the dye, in an appropriate solvent. Bathing methods, however, are not to be preferred ordinarily.

What we claim as: our invention and desire to is. 1. A compound selected rrom the group conslsting of those compounds which are represented by the ioliiowing general iormulasr and aralkyl group and .aryl: group; X. represents a member selected from the group consisting. of

an amino group, an alkylthio group-and an aralkylthio group, X1 represents an anion and R2 represents av member sel'ected'gromthe group consisting oranalkylandanaralkylgroun.

2. The compounds which-are represented by the following general formula:

wherein R represents; a 2-furylgroup, R represents a. member selected from the group consisting of a hydrogen atom, an alkylgroup an aralkyl. group, and an aryl group, and X represents a member selected 'from'the'gronp consisting of an amino. group, an 'aliryltliio group and anaralkylthio group; I V

3. A compound represented formula:

4-. The compounds represented by the follow mg general formula:

11( nn.o I 11-0 H wherein R" represents 'aoralkyl.

be secured byLetters Patent of theUnited States 7 10 5. The compound represented by the following 8. The quaternary salt represented by the folformula: lowing formula:

s s no on HO/ HG--CH HO H g g 15 osoE, 5 g a g csom o 6. The quaternary salts which are represented f, os 000113 by the following general formula: 0

1 EDWARD B. KNOTT. R'C FRANCES M. HAMER.

o-x l! RUSSELL J. RATHBONE.

15 REFERENCES CITED The following references are of record in the wherein R represents a 2-furyl roup, R reprefil f this patent; sents a member selected from the group consistv ing of a hydrogen atom, an alkyl group, an ar'al- UNITED STATES PATENTS kyl group and an aryl group, X represents a mem- 20 Number N Dat ber selected from the group consisting of an 2,213,986 Kendall Sept. 10, 1940 amino p, n lkyl hi r p and n r l- 2,302,112 Middleton Dec. 8, 1942 thio group, R2 represents a member selected from 2,423,709 Knott July 8, 1947 the group consisting of an alkyl group and an aralkyl group, and X1 represents an anion. 25 OTHER REFERENCES 7. The quaternary salt represented by the fol- Richters Organic Chemistry, vol. 3, pp. 12- lowing formula: 38.

s HGCH HG/ (lg p} a O-BCHI so H 

